The purpose of this project is to examine the acute and chronic responses of the pulmonary endothelium of rats or mice to three forms of lung injury: 1) ionizing radiation, 2) monocrotaline, and 3) bleomycin. The acute response of endothelial cells to ionizing radiation in situ also will be compared with that observed after irradiation of endothelial monolayers in vitro. Three indices of endothelial function will be monitored: 1) angiotensin converting enzyme (ACE) activity, 2) prostacyclin (PGI2) secretion, and 3) plasminogen activator activity. Functional changes in the pulmonary endothelium will be correlated with endothelial structure and ultrastructure. Interactions of the endothelium with formed elements in the blood, and with other cellular components of the lung will be emphasized in the electron micrographs. Structural and functional changes in the endothelium also will be related to whole organ function, as indicated by pulmonary arterial perfusion scans. To determine whether lung injury is accompanied by systemic changes, peripheral blood will be tested for the following: platelets, circulating platelet aggregates, prothrombin and partial thromboplastin times, fibrinogen, fibrin degradation products, aldosterone, corticonsterone, and ACE. Histologic evaluation of renal renin granules and the adrenal cortex will be performed. Right and left ventricular weight and wall thickness will be measured, as will pulmonary arteriolar wall thickness. Finally, we will determine whether the ACE inhibitor, Captopril, or the anti-inflammatory and collagen antagonist, D-penicillamine, can modify the pathogenesis of pulmonary injury in rodents. These data may identify mechanisms of pulmonary injury, particularly the role of endothelial damage therein, and may reveal steps at which intervention in the pathogenesis of lung injury may be accomplished in a clinically significant manner.